Role of XIST/miR-29a/LIN28A pathway in denatured dermis and human skin fibroblasts (HSFs) after thermal injury
Role of XIST/miR-29a/LIN28A pathway in denatured dermis and human skin fibroblasts (HSFs) after thermal injury
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XIST/miR-29a/LIN28A 通路在热损伤后变性真皮和人皮肤成纤维细胞 (HSF) 中的作用
DOI：
10.1002/jcb.26307
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发表时间：
2018-02-01
影响因子：
4
通讯作者：
Huang, Xiaoyuan
中科院分区：
文献类型：
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作者：
Guo, Le;Huang, Xu;Huang, Xiaoyuan
变性真皮是深度烧伤创面真皮的一部分，具有恢复正常形态和功能的能力。在我们之前的研究中，我们揭示了在变性真皮中miR-29 a的下调可能有助于烧伤创面愈合的后期阶段，并进一步促进I型胶原的合成。LIN 28 A是一种在胚胎发育过程中表达的高度保守的RNA结合蛋白，在发育、多能性、代谢以及成年组织修复中发挥作用。在本研究中，我们研究了LIN 28 A在人皮肤成纤维细胞（HSFs）和细胞外基质（ECM）中的功能作用，以及miR-29 a和LIN 28 A之间的相互作用。近年来，已报道长链非编码RNA在正常发育和生理以及疾病发展中起关键作用。利用在线工具筛选出了miR-29 a的几个候选lncRNA，其中XIST受miR-29 a的负调控。XIST是最早发现的肿瘤相关lncRNA之一，在多种生物学过程中发挥重要作用。此外，我们评估了XIST在HSF增殖、迁移和ECM合成中的作用和机制。通过调节miR-29 a/LIN 28 A，XIST敲低抑制HSF增殖、迁移和ECM合成。在变性真皮组织中，XIST和LIN 28 A表达上调，miR-29 a表达下调。因此，促进XIST在变性真皮中的表达，进而抑制miR-29 a和促进LIN 28 A的表达，进而促进HSF的增殖、迁移和ECM的合成，为变性真皮的修复提供了一种有前景的策略。
Denatured dermis is a part of the dermis in deep burn wound and has the ability to restore normal morphology and function. In our previous study, we revealed that miR-29a downregulation in denatured dermis may help burn wound healing in the later phase, and further enhance type I collagen synthesis. LIN28A, a highly-conserved RNA binding protein expressed during embryogenesis, plays roles in development, pluripotency, metabolism, as well as tissue repair in adults. In the present study, we investigated the functional roles of LIN28A in human skin fibroblasts (HSFs) and extracellular matrix (ECM), and the interaction between miR-29a and LIN28A. In recent years, long non-coding RNAs have been reported to play a key role in normal development and physiology, as well as in disease development. By using online tools, we screened out several candidate lncRNAs of miR-29a, among which XIST was inversely regulated by miR-29a. XIST, one of the first found cancer-associated lncRNAs, has been frequently reported to play major role in several biological processes. Further, we evaluated the roles and mechanism of XIST in HSF proliferation, migration, and ECM synthesis. Through regulation of miR-29a/LIN28A, XIST knockdown suppressed HSF proliferation, migration, and ECM synthesis. In denatured dermis tissues, XIST, and LIN28A expression was upregulated, miR-29a expression was downregulated. Taken together, promoting XIST expression in denatured dermis, thus to inhibit miR-29a and promote LIN28A expression, further promote HSF proliferation, migration, and ECM synthesis presents a promising strategy for denatured dermis repair.